Activation of phospholipase D by sphingoid bases in NG108-15 neural-derived cells.
Recent studies suggest that signal-dependent formation of phosphatidic acid by phospholipase D-catalyzed hydrolysis of phosphatidylcholine is a novel trans-membrane signaling pathway in mammalian cells. We here demonstrate that sphingosine, as well as some other long chain bases, activates phospholipase D in neural-derived NG108-15 cells. Sphingosine potently stimulated phosphatidic acid and, in the presence of ethanol, phosphatidylethanol formation. (Phosphatidylethanol is a nonphysiological phospholipid which is characteristically produced by phospholipase D in the presence of ethanol.) Elevated phosphatidic acid levels were accompanied by increased phosphatidylinositol and phosphatidylglycerol production and a decrease in diacylglycerol levels. Sphingosine stimulated phospholipase D activity in a time- and concentration-dependent manner. A long aliphatic chain and a free 2-amino group were important structural requirements for the activation of phospholipase D by sphingosine-related molecules. We propose that phospholipase D may constitute an important cellular target for sphingosine action under both physiological and pathological circumstances.
Lavie
Y
Y
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Liscovitch
M
M
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004075:Diglycerides / Q000378:metabolism; D005910:Glioma; D006822:Hybrid Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004075:Diglycerides; D010712:Phosphatidic Acids; D010743:Phospholipids; D010740:Phospholipases; D010739:Phospholipase D; D013110:Sphingosine